Current status of spent embryo media research for preimplantation genetic testing

Abstract

In recent years, a growing body of literature has emerged investigating the clinical utility of spent embryo media (SEM) for preimplantation genetic testing for aneuploidy (PGT-A) (Hammond et al. in Fertil Steril. 107(1):220-8, 2017; Xu et al. in Proc Natl Acad Sci USA. 113(42):11907-12, 2016; Shamonki et al. in Fertil Steril. 106(6):1312-8, 2016; Feichtinger et al. in Reprod BioMed Online. 34(6):583-9, 2017; Vera-Rodriguez et al. in Hum Reprod. 33(4):745-56, 2018; Kuznyetsov et al. in PLoS One. 13(5):e0197262, 2018; Ho et al. in Fertil Steril. 110(3):467-75, 2018; Capalbo et al. in Fertil Steril. 110(5):870-9, 2018). Most of these studies have reported moderate success rates, suggesting the need for improvements in sensitivity and specificity. The concordance between spent media and embryo biopsy or whole embryo was reported to be between 30.4 and 90%, with 50-70% correlation being the most representative (Xu et al. in Proc Natl Acad Sci USA. 113(42):11907-12, 2016; Shamonki et al. in Fertil Steril. 106(6):1312-8, 2016; Feichtinger et al. in Reprod BioMed Online. 34(6):583-9, 2017; Vera-Rodriguez et al. in Hum Reprod. 33(4):745-56, 2018; Kuznyetsov et al. in PLoS One. 13(5):e0197262, 2018; Ho et al. in Fertil Steril. 110(3):467-75, 2018). Here, we will analyze all spent media testing strategies including SEM collection methods, whole genome amplification (WGA) strategies, chromosome copy number detection, and bioinformatics analysis tools. We will propose improvements to further increase the accuracy and sensitivity of the assay before bringing PGT-A with SEM into the clinical sphere.

Keywords: Cell-free DNA; Non-invasive; PGT-A; Preimplantation genetic screening; Spent embryo media; cfDNA.